- Email: [email protected]
A new approach to condensed pyridines
, 2005, 15(4), 151–152
A new approach to condensed pyridines Mikhail M. Krayushkin,a Vladimir N. Yarovenko,a Igor P. Sedishev,a Anatoly A. Andreiko,b Nataliya N. Mochulskayac and Valery N. Charushin*b a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation. Fax: +7 095 137 6939; e-mail: [email protected] b I. Ya. Postovsky Institute of Organic Synthesis, Urals Branch of the Russian Academy of Sciences, 620219 Ekaterinburg, Russian Federation. Fax: +7 3433 74 1189; e-mail: [email protected] c Department of Organic Chemistry, Urals State Technical University, 620002 Ekaterinburg, Russian Federation. Fax: +7 3433 74 0458; e-mail: [email protected]
DOI: 10.1070/MC2005v015n04ABEH002142
The interaction of thiazolo[4,5-e][1,2,4]triazines with bicyclo[2.2.1]heptadiene at a high pressure (up to 15 kbar) results in the corresponding thiazolo[4,5-b]pyridines, and this is the key step of a new approach to fused pyridines based on the tandem SHN – SNH reactions on the 1,2,4-triazine ring. Pyridines and condensed systems bearing the pyridine ring are of considerable interest to chemists and biologists.1–5 These molecules are very important for medicinal chemistry, pharmaceutical industry, etc.1,2 Condensed systems, such as thieno-3 and thiazolopyridines,4,5 are of interest as biologically active compounds. In this paper, we describe a new methodology for the synthesis of condensed pyridines, which is based on the tandem SNH – SHN reactions on the 1,2,4-triazine ring followed by the triazine-to-pyridine ring transformation reaction. We have recently reported that the tandem nucleophilic addition (AN–AN) reactions of 3-aryl-1,2,4-triazines 1 with thioarylamides 2 in acetic anhydride proceed smoothly at room temperature resulting in the formation of 1,4,4a,7a-tetrahydrothiazolo[4,5-e][1,2,4]triazines 3 in good yields. Oxidation of adducts 3 with potassium permanganate in acetone gave aromatic H thiazolo[4,5-e][1,2,4]triazines 4 as a result of the tandem SH N – SN reaction (Scheme 1).6,7 1,2,4-Triazines are known to undergo inverse electron-demand Diels–Alder cycloaddition reactions with electron-rich dienophiles, thus being transformed into pyridines or pyrimidines.8–12 In continuation of our studies on the chemistry of 1,2,4-triazines, we studied the conversion of thiazolo[4,5-e][1,2,4]-
Me N
N
S Ar
N
Ph
AN–AN N
Ac2O
H2N
N
H S Ar
N
Ph 2
1
O
N H
H 3
H SH N–SN
N
KMnO4 acetone
Ph
N
S
N
N
Ar 4
Scheme 1
triazine 4a into thiazolopyridine 6 by the action of bicyclo[2.2.1]hepta-2,5-diene 5 (Scheme 2). The behaviour of 3-phenyl1,2,4-triaizine 1 towards dienophile 5 was studied for comparison. Our attempts to cause the ring transformation of thiazolo[4,5-e][1,2,4]triazine 4a by the action of 1-morpholinocyclo-
Mendeleev Commun. 2005
151
, 2005, 15(4), 151–152
N Ph
N
proceeding under high-pressure conditions (0.25–15 kbar). The reaction is a key step in the new synthesis of condensed pyridines based on the tandem SHN – SHN reactions on the 1,2,4-triazine ring.
S Cl
N
5
This work was supported by the US Civilian Research and Development Foundation and the Ministry of Education (grant no. REC-005, Y1-C-05-13) and the Russian Foundation for Basic Research (grant no. 04-03-96090).
N 4a S
References
Cl Ph
N
N
6 Scheme 2
hexene or bicyclo[2.2.1]hepta-2,5-diene 5 in refluxing dioxane at ambient pressure were unsuccessful. In all cases, the starting material, i.e., thiazolo[4,5-e][1,2,4]triazine 4a, was isolated. However, we found that the reaction of 6-(4-chlorophenyl)3-phenyl[1,3]thiazolo[4,5-e][1,2,4]triazine 4a with bicyclo[2.2.1]hepta-2,5-diene 5 in dichloromethane leads to the formation of thiazolo[4,5-b]pyridine 6 under high-pressure conditions (from 250 bar to 15 kbar) (Scheme 2). The yields of 6 are listed in Table 1. The best yield of thiazolo[4,5-b]pyridine 6 (95%) was reached at a pressure of 15 kbar and at 100 °C (Table 1, entry 4). Evidence for the structure of 6 is provided by 1H NMR spectroscopy and mass spectrometry.† The resonance signals of H-6 and H-7 of the pyridine ring are two doublets at 7.83 and 8.32 ppm with vicinal coupling 3J 8.4 Hz characteristic of ortho-protons. The peak of the molecular ion (M+) observed in the mass spectrum of compound 6 (M+, m/z 322) is in full agreement with the structure. For comparison, 3-phenyl-1,2,4-triazine 1 was found to react with 5 to 2-phenylpyridine in dichloromethane at 110 °C and 5 kbar in a nearly quantitative yield (98%). In conclusion, note that we have found the ability of the 1,2,4-triazine ring annelated with the electron-donating thiazole ring to be transformed into the corresponding thiazolo[4,5-b]pyridine via an inverse electron-demand Diels–Alder reaction
1 E. F. V. Scriven, J. E. Toomey, Jr. and R. Murugan, in Kirk-Othmer Encyclopedia of Chemical Technology, 4th edn., John Wiley & Sons, New York, 1996, vol. 20, pp. 641–679. 2 Comprehensive Heterocyclic Chemistry, eds. A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford–New York, 1984, vol. 2. 3 J. M. Barker, Adv. Heterocycl. Chem., 1977, 21, 65. 4 M. Matsuo, D. Morino and K. Tsuji, US Patent, 4885297 (Chem. Abstr., 1989, 111, 77996x). 5 A. Nakayashki and A. Shimokitazawa, Eur. Patent, 0277701 (Chem. Abstr., 1988, 110, 57654k). 6 V. N. Charushin, N. N. Mochulskaya, A. A. Andreiko, M. I. Kodess and O. N. Chupakhin, Mendeleev Commun., 2002, 28. 7 N. N. Mochulskaya, A. A. Andreiko, M. I. Kodess, E. B. Vasil’eva, V. I. Filyakova, A. T. Gubaidullin, I. A. Litvinov, O. G. Sinyashin, G. G. Aleksandrov and V. N. Charushin, Izv. Akad. Nauk, Ser. Khim., 2004, 1228 (Russ. Chem. Bull., Int. Ed., 2004, 53, 1279). 8 H. Neunhoeffer, in Comprehensive Heterocyclic Chemistry, eds. A. R. Katritzky and C. W. Rees, Pergamon Press, New York, 1984, vol. 3, p. 385. 9 E. C. Taylor, J. Org. Chem., 1987, 52, 4287. 10 V. N. Charushin, A. Veldhuizen, H. C. van der Plas and C. H. Stam, Tetrahedron, 1989, 45, 6499. 11 V. N. Charushin, S. G. Alexeev, O. N. Chupakhin and H. C. van der Plas, Adv. Heterocycl. Chem., 1989, 46, 73. 12 O. N. Chupakhin, S. G. Alexeev, B. V. Rudakov and V. N. Charushin, Heterocycles, 1992, 33, 931.
Table 1 Yields of thiazolo[4,5-b]pyridine 6 derived from the reaction of 4a with 5 in CH2Cl2 performed under high-pressure conditions (0.25–15 kbar) (the reaction time is 6 h). Yield (%) Entry 1 2 3 4 5 6 7 8 9
T/°C 100 100 100 100 150 150 150 175 175
P/kbar 0.25 5 10 15 0.25 5 10 0.25 5
Pyridine 6
Starting material 4a
— — 44 95 — 45 86 40 75
94 91 56 5 96 55 14 60 25
†
The 1H NMR spectrum of 6 in CDCl3 was recorded on a Bruker WP-250 instrument (250 MHz for 1H). The mass spectrum was recorded using a Varian MAT 311A spectrometer. A typical experimental procedure for the synthesis of 2-(4-chlorophenyl)-5-phenylthiazolo[4,5-b]pyridine 6. Bicyclo[2.2.1]hepta-2,5-diene 5 (405 mg, 4.4 mmol) was added to 6-(4-chlorophenyl)-3-phenyl[1,3]thiazolo[4,5-e][1,2,4]triazine 4 (100 mg, 0.308 mmol) in 15 ml (19.8 g) of dichloromethane. The reaction mixture was heated in a Teflon ampoule for 6 h under high-pressure conditions (Table 1). The solvent was evaporated to give a precipitate of 6 with mp 234.5–235 °C. MS, m/z (%): 322 (M+), 185 (M – CNPhCl), 153 (M – SCNPhCl). 1H NMR (250 MHz, CDCl ) d: 7.52 (m, 5H, H ), 7.83 (d, 1H, H , 3 Ar Py J 8.4 Hz), 8.20 (m, 4H, HAr), 8.32 (d, 1H, HPy, J 8.4 Hz).
152
Mendeleev Commun. 2005
Received: 24th February 2005; Com. 05/2465
A new approach to condensed pyridines Mikhail M. Krayushkin,a Vladimir N. Yarovenko,a Igor P. Sedishev,a Anatoly A. Andreiko,b Nataliya N. Mochulskayac and Valery N. Charushin*b a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation. Fax: +7 095 137 6939; e-mail: [email protected] b I. Ya. Postovsky Institute of Organic Synthesis, Urals Branch of the Russian Academy of Sciences, 620219 Ekaterinburg, Russian Federation. Fax: +7 3433 74 1189; e-mail: [email protected] c Department of Organic Chemistry, Urals State Technical University, 620002 Ekaterinburg, Russian Federation. Fax: +7 3433 74 0458; e-mail: [email protected]
DOI: 10.1070/MC2005v015n04ABEH002142
The interaction of thiazolo[4,5-e][1,2,4]triazines with bicyclo[2.2.1]heptadiene at a high pressure (up to 15 kbar) results in the corresponding thiazolo[4,5-b]pyridines, and this is the key step of a new approach to fused pyridines based on the tandem SHN – SNH reactions on the 1,2,4-triazine ring. Pyridines and condensed systems bearing the pyridine ring are of considerable interest to chemists and biologists.1–5 These molecules are very important for medicinal chemistry, pharmaceutical industry, etc.1,2 Condensed systems, such as thieno-3 and thiazolopyridines,4,5 are of interest as biologically active compounds. In this paper, we describe a new methodology for the synthesis of condensed pyridines, which is based on the tandem SNH – SHN reactions on the 1,2,4-triazine ring followed by the triazine-to-pyridine ring transformation reaction. We have recently reported that the tandem nucleophilic addition (AN–AN) reactions of 3-aryl-1,2,4-triazines 1 with thioarylamides 2 in acetic anhydride proceed smoothly at room temperature resulting in the formation of 1,4,4a,7a-tetrahydrothiazolo[4,5-e][1,2,4]triazines 3 in good yields. Oxidation of adducts 3 with potassium permanganate in acetone gave aromatic H thiazolo[4,5-e][1,2,4]triazines 4 as a result of the tandem SH N – SN reaction (Scheme 1).6,7 1,2,4-Triazines are known to undergo inverse electron-demand Diels–Alder cycloaddition reactions with electron-rich dienophiles, thus being transformed into pyridines or pyrimidines.8–12 In continuation of our studies on the chemistry of 1,2,4-triazines, we studied the conversion of thiazolo[4,5-e][1,2,4]-
Me N
N
S Ar
N
Ph
AN–AN N
Ac2O
H2N
N
H S Ar
N
Ph 2
1
O
N H
H 3
H SH N–SN
N
KMnO4 acetone
Ph
N
S
N
N
Ar 4
Scheme 1
triazine 4a into thiazolopyridine 6 by the action of bicyclo[2.2.1]hepta-2,5-diene 5 (Scheme 2). The behaviour of 3-phenyl1,2,4-triaizine 1 towards dienophile 5 was studied for comparison. Our attempts to cause the ring transformation of thiazolo[4,5-e][1,2,4]triazine 4a by the action of 1-morpholinocyclo-
Mendeleev Commun. 2005
151
, 2005, 15(4), 151–152
N Ph
N
proceeding under high-pressure conditions (0.25–15 kbar). The reaction is a key step in the new synthesis of condensed pyridines based on the tandem SHN – SHN reactions on the 1,2,4-triazine ring.
S Cl
N
5
This work was supported by the US Civilian Research and Development Foundation and the Ministry of Education (grant no. REC-005, Y1-C-05-13) and the Russian Foundation for Basic Research (grant no. 04-03-96090).
N 4a S
References
Cl Ph
N
N
6 Scheme 2
hexene or bicyclo[2.2.1]hepta-2,5-diene 5 in refluxing dioxane at ambient pressure were unsuccessful. In all cases, the starting material, i.e., thiazolo[4,5-e][1,2,4]triazine 4a, was isolated. However, we found that the reaction of 6-(4-chlorophenyl)3-phenyl[1,3]thiazolo[4,5-e][1,2,4]triazine 4a with bicyclo[2.2.1]hepta-2,5-diene 5 in dichloromethane leads to the formation of thiazolo[4,5-b]pyridine 6 under high-pressure conditions (from 250 bar to 15 kbar) (Scheme 2). The yields of 6 are listed in Table 1. The best yield of thiazolo[4,5-b]pyridine 6 (95%) was reached at a pressure of 15 kbar and at 100 °C (Table 1, entry 4). Evidence for the structure of 6 is provided by 1H NMR spectroscopy and mass spectrometry.† The resonance signals of H-6 and H-7 of the pyridine ring are two doublets at 7.83 and 8.32 ppm with vicinal coupling 3J 8.4 Hz characteristic of ortho-protons. The peak of the molecular ion (M+) observed in the mass spectrum of compound 6 (M+, m/z 322) is in full agreement with the structure. For comparison, 3-phenyl-1,2,4-triazine 1 was found to react with 5 to 2-phenylpyridine in dichloromethane at 110 °C and 5 kbar in a nearly quantitative yield (98%). In conclusion, note that we have found the ability of the 1,2,4-triazine ring annelated with the electron-donating thiazole ring to be transformed into the corresponding thiazolo[4,5-b]pyridine via an inverse electron-demand Diels–Alder reaction
1 E. F. V. Scriven, J. E. Toomey, Jr. and R. Murugan, in Kirk-Othmer Encyclopedia of Chemical Technology, 4th edn., John Wiley & Sons, New York, 1996, vol. 20, pp. 641–679. 2 Comprehensive Heterocyclic Chemistry, eds. A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford–New York, 1984, vol. 2. 3 J. M. Barker, Adv. Heterocycl. Chem., 1977, 21, 65. 4 M. Matsuo, D. Morino and K. Tsuji, US Patent, 4885297 (Chem. Abstr., 1989, 111, 77996x). 5 A. Nakayashki and A. Shimokitazawa, Eur. Patent, 0277701 (Chem. Abstr., 1988, 110, 57654k). 6 V. N. Charushin, N. N. Mochulskaya, A. A. Andreiko, M. I. Kodess and O. N. Chupakhin, Mendeleev Commun., 2002, 28. 7 N. N. Mochulskaya, A. A. Andreiko, M. I. Kodess, E. B. Vasil’eva, V. I. Filyakova, A. T. Gubaidullin, I. A. Litvinov, O. G. Sinyashin, G. G. Aleksandrov and V. N. Charushin, Izv. Akad. Nauk, Ser. Khim., 2004, 1228 (Russ. Chem. Bull., Int. Ed., 2004, 53, 1279). 8 H. Neunhoeffer, in Comprehensive Heterocyclic Chemistry, eds. A. R. Katritzky and C. W. Rees, Pergamon Press, New York, 1984, vol. 3, p. 385. 9 E. C. Taylor, J. Org. Chem., 1987, 52, 4287. 10 V. N. Charushin, A. Veldhuizen, H. C. van der Plas and C. H. Stam, Tetrahedron, 1989, 45, 6499. 11 V. N. Charushin, S. G. Alexeev, O. N. Chupakhin and H. C. van der Plas, Adv. Heterocycl. Chem., 1989, 46, 73. 12 O. N. Chupakhin, S. G. Alexeev, B. V. Rudakov and V. N. Charushin, Heterocycles, 1992, 33, 931.
Table 1 Yields of thiazolo[4,5-b]pyridine 6 derived from the reaction of 4a with 5 in CH2Cl2 performed under high-pressure conditions (0.25–15 kbar) (the reaction time is 6 h). Yield (%) Entry 1 2 3 4 5 6 7 8 9
T/°C 100 100 100 100 150 150 150 175 175
P/kbar 0.25 5 10 15 0.25 5 10 0.25 5
Pyridine 6
Starting material 4a
— — 44 95 — 45 86 40 75
94 91 56 5 96 55 14 60 25
†
The 1H NMR spectrum of 6 in CDCl3 was recorded on a Bruker WP-250 instrument (250 MHz for 1H). The mass spectrum was recorded using a Varian MAT 311A spectrometer. A typical experimental procedure for the synthesis of 2-(4-chlorophenyl)-5-phenylthiazolo[4,5-b]pyridine 6. Bicyclo[2.2.1]hepta-2,5-diene 5 (405 mg, 4.4 mmol) was added to 6-(4-chlorophenyl)-3-phenyl[1,3]thiazolo[4,5-e][1,2,4]triazine 4 (100 mg, 0.308 mmol) in 15 ml (19.8 g) of dichloromethane. The reaction mixture was heated in a Teflon ampoule for 6 h under high-pressure conditions (Table 1). The solvent was evaporated to give a precipitate of 6 with mp 234.5–235 °C. MS, m/z (%): 322 (M+), 185 (M – CNPhCl), 153 (M – SCNPhCl). 1H NMR (250 MHz, CDCl ) d: 7.52 (m, 5H, H ), 7.83 (d, 1H, H , 3 Ar Py J 8.4 Hz), 8.20 (m, 4H, HAr), 8.32 (d, 1H, HPy, J 8.4 Hz).
152
Mendeleev Commun. 2005
Received: 24th February 2005; Com. 05/2465